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Zhang J.,Zhengzhou University | Liu X.,Zhengzhou University | Liu X.,Fudan University | Lei X.,Fudan University | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010

Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC50 = 0.046, 0.869, and 1.375 μM, respectively) compared with luteolin 8 (EC50 = 1.45 ± 0.29 μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin. These luteolin derivatives represent a novel DAT agonist class, from which lead compounds useful for exploration of additional novel DAT agonists could be drawn. © 2010 Elsevier Ltd. All rights reserved. Source

Zhao G.,Cell Star Bio Technologies Co. | Zhao G.,CAS Shanghai Institutes for Biological Sciences | Qin G.-W.,CAS Shanghai Institute of Materia Medica | Gai Y.,Cell Star Bio Technologies Co. | And 2 more authors.
Chemical and Pharmaceutical Bulletin | Year: 2010

We previously reported that safflower (Carthamus tinctorius L.) ethyl acetate extract (HE) possessed an inhibitory action on serotonin (5HT) uptake in Chinese hamster ovary (CHO) cells expressing 5HT transporter (SERT) (S6 cells). Here, HE was adopted to go through an activity-guided isolation, and then an ingredient with potent SERT inhibitory action was obtained, which was elucidated as N1,N5-(Z)-N10-(E)-tri-p-coumaroylspermidine (CX), a new coumaroylspermidine analog, by using spectroscopic methods including extensive 1D- and 2D-NMR analyses. Preliminary pharmacological study demonstrated that CX was a potent SERT inhibitor. © 2010 Pharmaceutical Society of Japan. Source

Zhao G.,Cell Star Bio Technologies Co. | Zhao G.,CAS Shanghai Institutes for Biological Sciences | Wang J.,Cell Star Bio Technologies Co. | Qin G.-W.,CAS Shanghai Institutes for Biological Sciences | And 2 more authors.
Neurochemical Research | Year: 2010

Cynomorium songaricum Rupr. (SY) is a central nervous system-oriented herb material that has actions of anti-dementia, anti-epilepsy, and anti-stress. It is unclear whether SY would be biologically active in functionally regulating neurotransmitter transporters. Here, we assessed these potential actions using Chinese hamster ovary cells expressing γ-aminobutyric acid (GABA) transporter (GAT-1), dopamine transporter (DAT), norepinephrine transporter (NET), or serotonin transporter (SERT) (i.e. G1, D8, N1, or S6 cells, respectively). It was shown that SY extracts, such as SYw, SYa, SYp, SYc, SYe, and SYb (SY water, ethanol, petroleum ether, chloroform, ethyl acetate, and n-butyl alcohol extract, respectively) increased dopamine/norepinephrine (DA/NE) uptake by corresponding D8/N1 cells and decreased γ-aminobutyric acid/serotoin (GABA/5HT) uptake by corresponding G1/S6 cells; wherein, the potency or efficacy of SYc for up-regulating DA/NE uptake and that of SYb for inhibiting GABA/5HT uptake were relatively stronger. Additionally, GABA/5HTuptake inhibition by SY extracts were also seen in cortical synaptosomes, and DA/NE-uptake enhancement by SYc was dependent on the activity of DAT and NET. Thus, SY extracts especially SYc and SYb are novel neurotransmitter-transporter modulators functioning as DAT/ NET activators and/or GAT-1/SERT inhibitors. © Springer Science+Business Media, LLC 2009. Source

Zhao G.,Cell Star Bio Technologies Co. | Zhao G.,CAS Shanghai Institutes for Biological Sciences | Qin G.-W.,CAS Shanghai Institutes for Biological Sciences | Wang J.,Cell Star Bio Technologies Co. | And 3 more authors.
Neurochemistry International | Year: 2010

Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator. Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin. Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators. Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter. Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity. © 2009 Elsevier Ltd. All rights reserved. Source

Zhao G.,Cell Star Bio Technologies Co. | Zhao G.,CAS Shanghai Institutes for Biological Sciences | Zang S.-Y.,Cell Star Bio Technologies Co. | Zang S.-Y.,CAS Shanghai Institutes for Biological Sciences | And 12 more authors.
Journal of Nutritional Biochemistry | Year: 2011

Oxidative stress-induced neuronal cell death has been implicated in neurodegenerative diseases; one such disease is ischemic stroke. Using reactive oxygen species (ROS)-insulted primary neurons, we screened neuroprotectants with clinical potential and then, using ischemia/reperfusion (I/R) model, investigated the anti-ischemic potential of candidate neuroprotectants. Here, we showed that luteolin, isolated from the ripe fruit of . Perilla frutescens (L.) Britt, exhibited a neuroprotective action upon the in vitro platform, thus serving as candidate for in vivo pharmacological evaluation. Liposome-encapsulated luteolin produced dramatic preventing effects on I/R-induced behavioral and histological injuries after a 13-day post-ischemic treatment. Furthermore, this phytochemical not only lowered the increased level of mitochondrial ROS but also substantially up-regulated the decreased activity of catalase and glutathione in I/R rat brains. Collectively, luteolin as a neuroprotectant acts by anti-ischemic activity likely through a rebalancing of pro-oxidant/antioxidant status. Its multitarget mechanisms implicate potential effectiveness for clinically treating ischemia stroke. © 2011 Elsevier Inc. Source

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